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Journal of Ovarian Research
Published in: Journal of Ovarian Research 1/2016

Open Access 01-12-2016 | Research

Long-term treatment with testosterone alters ovary innervation in adult pigs

Authors: Barbara Jana, Karolina A. Meller, Michał Bulc, Jarosław Całka

Published in: Journal of Ovarian Research | Issue 1/2016

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Abstract

Background

Intraovarian distribution and density of nerve fibres immunoreactive (IR) to protein gene product 9.5 (PGP 9.5) and containing dopamine-β-hydroxylase (DβH), neuropeptide Y (NPY), somatostatin (SOM), galanin (GAL) were determined.

Methods

From day 4 of the first oestrous cycle to day 20 of the second studied cycle, experimental gilts (n = 3) were injected with testosterone (T), while control gilts (n = 3) received corn oil.

Results

After T administration the numbers of fibres IR to PGP 9.5 and fibres IR to DβH, NPY and SOM were decreased. Fewer PGP 9.5- and DβH-IR terminals were observed within the ground plexus and around arteries and medullar veins, and medium tertiary follicles, and DβH-IR terminals in the vicinity of small tertiary follicles. T decreased the density of NPY-IR fibres in the medullar part of the ground plexus, and SOM-IR in the cortical part of the ground plexus.

Conclusions

The obtained data show that long-term T treatment of gilts decreases the total number of intraovarian fibres, including sympathetic ones. These results suggest that elevated T levels that occur during pathological states may affect the innervation pattern of ovaries, and their function(s).
Literature
1.
Panidis D, Farmakiotis D, Rousso D, Katsikis I, Kourtis A, Diamanti-Kandarakis E. Serum luteinizing hormone levels are markedly increased and significantly correlated with Delta 4-androstenedione levels in lean women with polycystic ovary syndrome. FertilSteril. 2005;84:538–40.
2.
Keefe CC, Goldman MM, Zhang K, Clarke N, Reitz RE, Welt CK. Simultaneous measurement of thirteen steroid hormones in women with polycystic ovary syndrome and control women using liquid chromatography-tandem mass spectrometry. PLoS One. 2014;9:e93805.CrossRefPubMedPubMedCentral
3.
Singh P, Deleon F, Anderson R. Steroid cell ovarian neoplasm, not otherwise specified: a case report and review of the literature. Case Rep Obstet Gynecol. 2012;2012:253152.PubMedPubMedCentral
4.
Goodarzi MO, Dawson DW, Li X, Lei Z, Shintaku P, Rao CV, Van Herle AJ. Virilization in bilateral macronodular adrenal hyperplasia controlled by luteinizing hormone. J Clin Endocrinol Metab. 2003;88:73–7.CrossRefPubMed
5.
Marcondes JA, Barcellos CR, Rocha MP, Bisi H. Changing pattern of gonadotropins in a patient with an adrenal-androgen secreting tumor. Clinics (Sao Paulo). 2011;66:355–7.CrossRef
6.
Varma T, Panchani R, Goyal A, Maskey R. A case of androgen-secreting adrenal carcinoma with non-classical congenital adrenal hyperplasia. Indian J Endocrinol Metab. 2013;17:243–5.CrossRef
7.
Jana B, Kucharski J, Ziecik AJ. Effect of intrauterine infusion of Escherichia coli on hormonal patterns in gilts during the oestrous cycle. Reprod Nutr Dev. 2004;44:37–48.CrossRefPubMed
8.
Szulańczyk-Mencel K, Rzasa A, Bielas W. Relationships between ovarian cysts and morphological and hormonal state of ovarian cortex in sows. Anim Reprod. 2010;121:273–8.CrossRef
9.
Hill KE, Scott-Moncrieff JC, Koshko MA, Glickman LT, Glickman NW, Nelson RW, Blevins WE, Oliver JW. Secretion of sex hormones in dogs with adrenal dysfunction. J Am Vet Med Assoc. 2005;226:556–61.CrossRefPubMed
10.
Majewski M. Afferent and efferent innervation of the porcine ovary-sources of origin and chemical coding. Acta Acad Agric Tech Olst, Veterinaria. 1997;Suppl B 24:3–125. In Polish.
11.
Jana B, Majewski M. Influence of the peripheral nervous system on ovarian function. Medycyna Wet. 2007;63:1163–7 (In Polish).
12.
Barreca A, Valli B, Cesarone A, Arvigo M, Balasini M, Battista La Sala G, Garrone S, Minuto F, Giordano G. Effects of the neuropeptide Y on estradiol and progesterone secretion by human granulosa cells in culture. Fertil Steril. 1998;70:320–5.CrossRefPubMed
13.
Sosa ZY, Casais M, Rastrilla AM, Aguado L. Adrenergic influences on coeliac ganglion affect the release of progesterone from cycling ovaries: characterization of an in vitro system. J Endocrinol. 2000;166:307–18.CrossRefPubMed
14.
Miyamoto A, Brückmann A, von Lützow H, Schams D. Multiple effects of neuropeptide Y, substance P and vasoactive intestinal polypeptide on progesterone and oxytocin release from bovine corpus luteum in vitro. J Endocrinol. 1993;138:451–8.CrossRefPubMed
15.
Pitzel L, Jarry H, Wuttke W. Effects of substance-P and neuropeptide-Y on in vitro steroid release by porcine granulosa and luteal cells. Endocrinology. 1991;129:1059–65.CrossRefPubMed
16.
Andreani CL, Lazzarin N, Pierro E, Lanzone A, Mancuso S. Somatostatin action on rat ovarian steroidogenesis. Hum Reprod. 1995;10:1968–73.PubMed
17.
Xu XJ, Hao JX, Wiesenfeld-Hallin Z, Håkanson R, Folkers K, Hökfelt T. Spantide II, a novel tachykinin antagonist, and galanin inhibit plasma extravasation induced by antidromic C-fiber stimulation in rat hindpaw. Neuroscience. 1991;42:731–7.CrossRefPubMed
18.
Markiewicz W, Jaroszewski JJ, Barszczewska B, Sienkiewicz W. Localization of neuropeptide Y and norepinephrine in the porcine ovarian artery and their influence on the local blood pressure. Folia Histochem Cytobiol. 2003;41:73–81.PubMed
19.
Keator CS, Custer EE, Hoagland TA, Schreiber DT, Mah K, Lawsom AM, Slayden OD, McCraken JA. Evidence for a potential role of neuropeptide Y in ovine corpus luteum function. Dom Anim Endorcinol. 2010;38:103–14.CrossRef
20.
Traurig HH, Papka RE. Autonomic efferent and visceral sensory innervation of the female reproductive system: special reference to the functional roles of nerves in reproductive organs. In: Maggi CA, editor. Nervous control of the urogenital system. Chur, Switzerland: Harwood Academic Press; 1993. p. 103–41.
21.
Curry Jr TE, Lawrence Jr IE, Burden HW. Ovarian sympathectomy in the guinea pig. I. Effects on follicular development during the estrous cycle. Cell Tissue Res. 1984;236:257–63.CrossRefPubMed
22.
Nestorović N, Manojlović-Stojanoski M, Ristić N, Sekulić M, Sošić-Jurjević B, Filipović B, Milošević V. Somatostatin-14 influences pituitary-ovarian axis in peripubertal rats. Histochem Cell Biol. 2008;130:699–708.CrossRefPubMed
23.
24.
Lara HE, Ferruz JL, Luza S, Bustamante DA, Borges Y, Ojeda SR. Activation of ovarian sympathetic nerves in polycystic ovary syndrome. Endocrinology. 1993;133:2690–5.PubMed
25.
Lara HE, Dissen GA, Leyton V, Paredes A, Fuenzalida H, Fiedler JL, Ojeda SR. An increased intraovarian synthesis of nerve growth factor and its low affinity receptor is a principal component of steroid-induced polycystic ovary in the rat. Endocrinology. 2000;141:1059–72.PubMed
26.
Rosa-E-Silva A, Guimaraes MA, Padmanabhan V, Lara HE. Prepubertal administration of estradiol valerate disrupts cyclicity and leads to cystic ovarian morphology during adult life in the rat: role of sympathetic innervation. Endocrinology. 2003;144:4289–97.CrossRefPubMed
27.
Shinohara Y, Matsumoto A, Mori T. Effects of prenatal exposure to diethylstilbestrol on the sympathetic nervous system in the rat ovary. Neurosci Lett. 1998;255:123–6.CrossRefPubMed
28.
Shinohara Y, Matsumoto A, Hayashi S, Mori T. Prenatal exposure to diethylstilbestrol decreases the number of estrogen receptor alpha-containing neurons innervating the ovary in rat celiac ganglion. Neuroscience. 2000;101:779–83.CrossRefPubMed
29.
Lakomy M, Kaleczyc J, Całka J. The effect of oestradiolum benzoicum and progesterone on AChE activity in the nerves of the female reproductive system of immature pigs. Gegenbaurs Morphol Jahrb. 1986a;132:333–48.
30.
Lakomy M, Kotwica J, Całka J, Kaleczyc J. The effect of oestradiolum benzoicum and progesterone on the noradrenaline content in organs of the female reproductive system of sexually immature pigs. Gegenbaurs Morphol Jahrb. 1986b;132:129–43.
31.
Koszykowska M, Całka J, Gańko M, Jana B. Long-term estradiol-17β administration reduces population of neurons in the sympathetic chain ganglia supplying the ovary in adult gilts. Exp Mol Pathol. 2011;91:353–61.CrossRefPubMed
32.
Koszykowska M, Całka J, Szwajca P, Jana B. Long-term estradiol-17β administration decreases the number of neurons in the caudal mesenteric ganglion innervating the ovary in sexually mature gilts. J Reprod Dev. 2011;57:62–71.CrossRefPubMed
33.
Jana B, Lata M, Bulc M, Całka J. Long term estradiol-17β administration changes population of the dorsal root ganglia neurons innervating the ovary in the sexually mature gilts. Neuropeptides. 2012;46:157–65.CrossRefPubMed
34.
Jana B, Palus K, Czarzasta J, Całka J. Long-term estradiol-17β administration changes population of paracervical ganglion neurons supplying the ovary in adult gilts. J Mol Neurosci. 2013;50:424–33.CrossRefPubMed
35.
Koszykowska M, Całka J, Nidzgorska A, Jana B. Exogenous long-term treatment with 17β-oestradiol alters the innervation pattern in pig ovary. Reprod Fertil Dev. 2013;25:661–73.CrossRefPubMed
36.
Vallcaneras SS, Casais M, Delgado SM, Filippa V, Mohamed F, Sosa Z, Rastrilla AM. Androgen receptors in coeliac ganglion in late pregnant rat. Steroids. 2009;74:526–34.CrossRefPubMed
37.
Vallcaneras SS, Casais M, Anzulovich AC, Delgado SM, Sosa Z, Telleria CM, Rastrilla AM. Androstenedione acts on the coeliac ganglion and modulates luteal function via the superior ovarian nerve in the postpartum rat. J Steroid Biochem Mol Biol. 2001;125:243–50.CrossRef
38.
Verma N, Rettenmeier AW, Schmitz-Spanke S. Recent advances in the use of Susscrofa (pig) as a model system for proteomic studies. Proteomics. 2011;11:776–93.CrossRefPubMed
39.
Swindle MM, Makin A, Herron AJ, Clubb Jr FJ, Frazier KS. Swine as models in biomedical research and toxicology testing. Proc Natl Acad Sci U S A. 2012;109:16612–7.CrossRef
40.
Jana B, Rytel L, Czarzasta J, Całka J. Reduction of the number of neurons in the caudal mesenteric ganglion innervating the ovary in sexually mature gilts following testosterone administration. J Neuroendocrinol. 2013;25:826–38.CrossRefPubMed
41.
Jana B, Całka J, Bulc M, Czarzasta J. Long-term testosterone administration affects the number of paracervical ganglion ovary-projecting neurons in sexually mature gilts. Neurosc Res. 2014;83:89–96.CrossRef
42.
Jana B, Całka J, Rytel L, Czarzasta J. Morphological and neurochemical characterization of the ovarian sympathetic chain ganglia perikarya in testosterone-treated sexually matured pigs. Ann Anat. 2015;202:28–35.CrossRefPubMed
43.
Majewski M, Heym C. The origin of ovarian neuropeptide Y (NPY)-immunoreactive nerve fibres from the inferior mesenteric ganglion in the pig. Cell Tissue Res. 1991;266:591–6.CrossRefPubMed
44.
Wulff C, Wilson H, Wiegand SJ, Rudge JS, Fraser HM. Prevention of thecal angiogenesis, antral follicular growth, and ovulation in the primate by treatment with vascular endothelial growth factor trap R1R2. Endocrinology. 2002;143:2797–807.CrossRefPubMed
45.
Barboni B, Martelli A, Berardinelli P, Russo V, Turriani M, Bernabò N, Lucidia P, Mattioli M. Ovarian follicle vascularization in fasted pig. Theriogenology. 2004;62:943–97.CrossRefPubMed
46.
Pieper DR, Gala RR, Schiff MA, Regiani SR, Marshall JC. Pituitary gonadotropin-releasing hormone (GnRH) receptor responses to GnRH in hypothalamus-lesioned rats: inhibition of responses by hyperprolactinemia and evidence that testosterone and estradiol modulate gonadotropin secretion at postreceptor sites. Endocrinology. 1984;115:1190–6.CrossRefPubMed
47.
Ziecik AJ, Britt HJ, Esbenshade KL. Short loop feedback of estrogen-induced luteinizing hormone surge in pigs. Endocrinology. 1988;122:1653–62.CrossRef
48.
Sullivan SD, Moenter SM. GABAergic integration of progesterone and androgen feedback to gonadotropin-releasing hormone neurons. Biol Reprod. 2005;72:33–41.CrossRefPubMed
49.
Zoubina EV, Smith PG. Sympathetic hyperinnervation of the uterus in the estrogen receptor alpha knock-out mouse. Neuroscience. 2001;103:237–44.CrossRefPubMed
50.
Ting AY, Blacklock AD, Smith PG. Estrogen regulates vaginal sensory and autonomic nerve density in the rat. Biol Reprod. 2004;71:1397–404.CrossRefPubMed
51.
Blacklock AD, Smith PG. Estrogen increases calcitonin gene-related peptide-immunoreactive sensory innervation of rat mammary gland. J Neurobiol. 2004;59:192–204.CrossRefPubMed
52.
Blacklock AD, Cauveren JA, Smith PG. Estrogen selectively increases sensory nociceptor innervation of arterioles in the female rat. Brain Res. 2004;1018:55–65.CrossRefPubMed
53.
Pelletier G, Ouellet J, Martel C, Labrie F. Androgenic action of dehydroepiandrosterone (DHEA) on nerve density in the ovariectomized rat vagina. J Sex Med. 2013;10:1908–14.CrossRefPubMed
54.
Sharma U, Dunphy G, Ely D. Testosterone increased blood pressure and decreased renal tyrosine hydroxylase activity in SHR/y and Wistar-Kyoto rats. Clin Exp Hypertens. 2002;24:141–53.CrossRefPubMed
55.
Kaur G, Janik J, Isaacson LG, Callahan P. Estrogen regulation of neurotrophin expression in sympathetic neurons and vascular targets. Brain Res. 2007;1139:6–14.CrossRefPubMed
56.
Anesetti G, Lombide P, Chávez-Genaro R. Prepubertal estrogen exposure modifies neurotrophin receptor expression in celiac neurons and alters ovarian innervation. Auton Neurosci. 2009;145:35–43.CrossRefPubMed
57.
Szatkowska C, Lakomy M. Adrenergic innervation of swine ovaries in various periods of pregnancy. Pol Arch Weter. 1987;27:73–80.PubMed
58.
59.
Pessina MA, Hoyt Jr RF, Goldstein I, Traish AM. Differential effects of estradiol, progesterone, and testosterone on vaginal structural integrity. Endocrinology. 2006;147:61–9.CrossRefPubMed
60.
Rodríguez R, Pozuelo JM, Martín R, Arriazu R, Santamaria L. Stereological quantification of nerve fibers immunoreactive to PGP 9.5, NPY, and VIP in rat prostate during postnatal development. J Androl. 2005;26:197–204.CrossRefPubMed
61.
62.
Duda M, Slomczyńska M. Immunohistochemical localization of androgen receptor in two subpopulations of porcine granulosa cells in vitro. Reprod Domest Anim. 2007;42:22–5.CrossRefPubMed
63.
Knapczyk K, Duda M, Durlej M, Galas J, Koziorowski M, Slomczynska M. Expression of estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta) in the ovarian follicles and corpora lutea of pregnant swine. Domest Anim Endocrinol. 2008;35:170–9.CrossRefPubMed
64.
Siminoski K, Bernanke J, Kay C, Murphy RA. Steroids and triiodothyronine reduce nerve growth factor concentrations in medium conditioned by L-929 fibroblasts. Endocrinology. 1986;118:1417–25.CrossRefPubMed
65.
Persson H, Ayer-Le Lievre C, Söder O, Villar MJ, Metsis M, Olson L, Ritzen M, Hökfelt T. Expression of beta-nerve growth factor receptor mRNA in Sertoli cells downregulated by testosterone. Science. 1990;247:704–7.CrossRefPubMed
66.
Hasan W, Smith HJ, Ting AY, Smith PG. Estrogen alters trkA and p75 neurotrophin receptor expression within sympathetic neurons. J Neurobiol. 2005;65:192–204.CrossRefPubMed
Metadata
Title
Long-term treatment with testosterone alters ovary innervation in adult pigs
Authors
Barbara Jana
Karolina A. Meller
Michał Bulc
Jarosław Całka
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2016
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/s13048-016-0273-4

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